Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2013-11-02
    Description: We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975283/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975283/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McConnell, Michael J -- Lindberg, Michael R -- Brennand, Kristen J -- Piper, Julia C -- Voet, Thierry -- Cowing-Zitron, Chris -- Shumilina, Svetlana -- Lasken, Roger S -- Vermeesch, Joris R -- Hall, Ira M -- Gage, Fred H -- DP2 OD006493/OD/NIH HHS/ -- DP20D006493-01/DP/NCCDPHP CDC HHS/ -- HHSN2752009000011C/PHS HHS/ -- N01-HD-9-011/HD/NICHD NIH HHS/ -- R01 MH095741/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 1;342(6158):632-7. doi: 10.1126/science.1243472.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179226" target="_blank"〉PubMed〈/a〉
    Keywords: Aneuploidy ; *DNA Copy Number Variations ; Frontal Lobe/*cytology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Male ; *Mosaicism ; Neural Stem Cells/*cytology ; Neurogenesis ; Neurons/*cytology ; Sequence Analysis, DNA ; Sequence Deletion ; Single-Cell Analysis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2015-11-03
    Description: Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742055/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742055/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mertens, Jerome -- Wang, Qiu-Wen -- Kim, Yongsung -- Yu, Diana X -- Pham, Son -- Yang, Bo -- Zheng, Yi -- Diffenderfer, Kenneth E -- Zhang, Jian -- Soltani, Sheila -- Eames, Tameji -- Schafer, Simon T -- Boyer, Leah -- Marchetto, Maria C -- Nurnberger, John I -- Calabrese, Joseph R -- Odegaard, Ketil J -- McCarthy, Michael J -- Zandi, Peter P -- Alda, Martin -- Nievergelt, Caroline M -- Pharmacogenomics of Bipolar Disorder Study -- Mi, Shuangli -- Brennand, Kristen J -- Kelsoe, John R -- Gage, Fred H -- Yao, Jun -- MH106056/MH/NIMH NIH HHS/ -- R01 MH106056/MH/NIMH NIH HHS/ -- U01 MH092758/MH/NIMH NIH HHS/ -- U01 MH92758/MH/NIMH NIH HHS/ -- England -- Nature. 2015 Nov 5;527(7576):95-9. doi: 10.1038/nature15526. Epub 2015 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Stem Cell Core, La Jolla, California 92037, USA. ; Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. ; Department of Psychiatry, Indiana University, Indianapolis, Indiana 46202, USA. ; Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio 44106, USA. ; Department of Psychiatry, University of Bergen, Bergen 5020, Norway. ; Department of Psychiatry, VA San Diego Healthcare System, La Jolla, California 92151, USA. ; Department of Psychiatry, University of California San Diego, La Jolla, California, 92093, USA. ; Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland 21218, USA. ; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, B3H2E2, Canada. ; Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA. ; Jiangsu Collaborative Innovation Center for Language Ability, Jiangsu Normal University, Xuzhou 221009, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26524527" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/*drug effects ; Antipsychotic Agents/*pharmacology ; Bipolar Disorder/*pathology ; Calcium Signaling/drug effects ; Dentate Gyrus/drug effects/pathology ; Endophenotypes ; Humans ; Induced Pluripotent Stem Cells/pathology ; Lithium Compounds/*pharmacology ; Male ; Mitochondria/pathology ; Neurons/*drug effects/*pathology ; Patch-Clamp Techniques
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2011-04-15
    Description: Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80-85%. Although post-mortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD, the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (Supplementary Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cyclic AMP and WNT signalling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood. We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392969/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392969/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brennand, Kristen J -- Simone, Anthony -- Jou, Jessica -- Gelboin-Burkhart, Chelsea -- Tran, Ngoc -- Sangar, Sarah -- Li, Yan -- Mu, Yangling -- Chen, Gong -- Yu, Diana -- McCarthy, Shane -- Sebat, Jonathan -- Gage, Fred H -- P01 NS028121/NS/NINDS NIH HHS/ -- P30 NS072031/NS/NINDS NIH HHS/ -- R01 MH083911/MH/NIMH NIH HHS/ -- England -- Nature. 2011 May 12;473(7346):221-5. doi: 10.1038/nature09915. Epub 2011 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21490598" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Antipsychotic Agents/pharmacology ; Cell Differentiation ; Cells, Cultured ; Cellular Reprogramming/genetics ; Child ; Female ; Fibroblasts/cytology ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Loxapine/pharmacology ; Male ; Membrane Proteins/metabolism ; Models, Biological ; Neurites ; Neurons/*cytology/drug effects/*metabolism ; Phenotype ; Pluripotent Stem Cells/*cytology/*metabolism/pathology ; Receptors, Glutamate/metabolism ; Schizophrenia/*pathology ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2015-11-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mertens, Jerome -- Wang, Qiu-Wen -- Kim, Yongsung -- Yu, Diana X -- Pham, Son -- Yang, Bo -- Zheng, Yi -- Diffenderfer, Kenneth E -- Zhang, Jian -- Soltani, Sheila -- Eames, Tameji -- Schafer, Simon T -- Boyer, Leah -- Marchetto, Maria C -- Nurnberger, John I -- Calabrese, Joseph R -- Oedegaard, Ketil J -- McCarthy, Michael J -- Zandi, Peter P -- Alda, Martin -- Nievergelt, Caroline M -- Pharmacogenomics of Bipolar Disorder Study -- Mi, Shuangli -- Brennand, Kristen J -- Kelsoe, John R -- Gage, Fred H -- Yao, Jun -- England -- Nature. 2016 Feb 11;530(7589):242. doi: 10.1038/nature16182. Epub 2015 Nov 25.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26605530" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-12-14
    Description: To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type–specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type–specific disease risk vulnerabilities in spatial genome organization.
    Keywords: Genetics, Neuroscience, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...